This renewal of the Specialized Neuroscience Research Program (SNRP) is based on commitments made by Howard University and the College of Medicine which guarantee long-term support toward the goal of developing talented minority neuroscientists. During SNRP-1 we developed an extensive research infrastructure, established multiple inter-departmental and inter-institutional research collaborations, and accomplished significant goals in interdisciplinary research. These achievements were crucial to the process by which we were able to attract three new project leaders to participate in the renewal of this program, (SNRP-2). In phase one of the SNRP, we focused on neuronal networks regulating breathing and the airway functions that are coupled to systems involved in behavioral state control. The current three interrelated projects seek to better understand how structural, functional, or genetic alterations in neuronal networks affect cardiovascular functions, aging, and cognition. Dr. Davila-Garcia's Project will use ultrastructural, electrocardiographic, echocardiographic, and physiological methods in the cat to define selected intrinsic cardiac neural mechanisms mediating parasympathetic control of ventricular functions. These novel studies will provide the first detailed analyses of the functional roles and neuroanatomical circuits of ventricular ganglia which mediate vagal effects on either or both ventricles of the heart. The resulting data will have important implications for understanding diseases such as congestive heart failure and pulmonary hypertension. The overall goal of Dr. Duttaroy's Project is to use the Drosophila model to understand the mechanistic basis of an oxidative damage protection system and how it is devoted towards maintaining the integrity of the nervous system, cognition, and neuromuscular ability as a function of age. Dr. Manaye's Project will utilize a well established mouse model of oxidative stress, the double transgenic expression of toxic beta-amyloid (Abeta), in combination with state-of the-art neurostereological techniques, to characterize age- and gender-related alterations in noradrenergic pathways innervating the amygdala, hippocampus, and frontal cortex. These studies will test the hypothesis that the age-related accumulation of toxic proteins related to Alzheimer's disease cause a cascade of neuroinflammatory responses leading to progressive degeneration of noradrenergic pathways responsible for cognitive and affective neurological functions. Administrative Core (Core A) will maintain centralized financial record keeping, prepare financial and scientific reports, facilitate the use of common resources, and monitor scientific progress. Neurobiology Core will provide central facilities, facilitate standardization of anatomical, neurochemical, molecular, physiological, and pharmacological methods, and assure uniform criteria for data analysis. Each project in this proposal for renewal arises directly from on-going work in our laboratories at Howard University. The overall program will provide new knowledge on plasticity of neuronal networks that regulate autonomic functions, behavioral state control, and cognition.